UW research: Will mapping parents’ DNA help offspring or just freak people out?

Photo from “Genome: Unlocking Life’s Code” exhibit at the Smithsonian National Museum of Natural History.

The more we learn about mutations in our DNA, the more it seem like we’re running around in a dark room littered with sharp objects … and it’s just a matter of time before a baby gets loose in there!

University of Washington researchers want to find out if all this knowledge does us any good.

Whole genome analysis – a complete picture of our DNA and the mutations in it that could cause disease – is becoming a widespread, affordable a tool in medicine’s arsenal. A few years ago, billions were spent mapping the first one, and now a full mapping runs about five grand – soon it will be $1,000, or less.

Doctors and their patients already test for specific genes to tell them about potential health problems that could be in store for the patient. Quite famously, Angelina Jolie recently had her breast tissue removed because she tested positive for a genetic marker for breast cancer.

Just think what preventative action we might undertake when we know our entire DNA package. We can prepare early for heart disease, Alzheimer’s or prepare our family for the birth of child who will have special needs. Or, not have that birth.

Then, factor in the power of not only knowing your genetic makeup or that of your child, but knowing the genes of your mate even before you set out to conceive. Talk about your tangled webs.

Well, this is the territory in which several UW scientists and their peers will be spending $27 million from the National Institutes of Health doing not only whole genome analysis, but also trying to figure out whether that analysis does any good when it comes to making babies.

“The areas of research being pursued by these new projects include [1] using genome sequencing to inform couples about reproductive risks, [2] determining the genetic causes of childhood developmental delays and communicating findings to parents, and [3] detecting genomic alterations that can lead to cancer,” NIH reported.

The fourth grant went to four UW scientists – Gail Jarvik, Wylie Burke, Debbie Nickerson and Peter Tarczy-Hornoch – who are tasked with organizing the teams and interpreting results from the studies.

One of the more novel and open-ended studies involves testing couples planning to have a child. These couples will come from a pool of patients at the Kaiser Permanente Center in Portland.

Related: Take our polls at the bottom of this story!

“Carrier testing” or looking for genetic markers for specific diseases is nothing new, explained Dr. Ben Wilfond, a UW pediatric bioethics expert at Seattle Children’s Research Institute. Doctors have been testing potential parents for gene mutations that can result in diseases such as Tay-Sachs, Canavan, sickle cell anemia and cystic fibrosis for, in some cases, decades.

And one thing this history has taught researchers is that “the idea of carrier testing is not benign,” Wilfond said.

“It may be helpful to people for making decisions but if it’s misunderstood, it causes problems for them as well as everybody else,” he explained.

Problems range from being denied insurance to worries that the testing could lead to a reduction of births in a specific race – such as testing for sickle cell, which predominantly affects African Americans.

The testing can look like eugenics to some: Having fewer people with the sickle cell means having fewer people of the race mostly affected by the disease.

In fact, Wilfond explained, there are two ways of looking at why those tests are offered.

One, “we want people to make decisions that are right for themselves.” The tests can help a person make choices about his or her own life or prepare a child for the onset of a disease.

The second reason involves not bringing people into this world with the disease: “Boy this is really a horrible disease and wouldn’t we all be better off if people with this disease were not around.”

What’s the whole genome analysis effect?

Helping potential parents wade through these issues when it comes to testing for specific genes is one thing, but throwing in the potential to discover any number of hundreds of gene mutations that could lead to diseases is another thing.

“There are all these companies doing carrier testing and probably someone is going to offer genome sequencing for carrier testing,” Wilfond said. “So, wouldn’t it be better if we had a research project around this to learn how this plays out.”

Will those tests help people understand their risks better or just make them more confused?

After all, even if both potential parents test positive for a mutation that leads to a disease, the child still has a better than even chance of not getting the mutation. In order for a child to develop one of these diseases, both parents have to pass a copy of the mutation.

“There are still a lot of questions about how to use whole genome sequencing in clinical practice,” said genetic epidemiologist Katrina Goddard, the other principle researcher in the Kaiser study.

“We don’t know yet if this is the best way to predict genetic risk, and we don’t know what impact the information will have on the couples and their families,” she said in a news release. “These are the questions we hope to answer in our study.”

Do it, do it now!

“We have to do research up front,” Wilfond said of NIH’s motivation for spending money on these issues. “We can’t just start adding new things to health care without knowing what the effects are going to be.”

Even before the researchers in this study start drawing blood from potential parents, they’re trying to establish a range of potential results from that genome analysis to share with them. The researchers themselves will only be looking for 120 of the many varieties of conditions.

The diseases that could result from mutations range from the very worst and most deadly to ones that “only” cause bad eyesight or hearing loss.

So, right now the researchers are trying to establish the four or five categories of diseases people can chose to be told exist or don’t in their DNA.

“Do you want to have whole genome sequencing for these really serious conditions, or these conditions plus the middle-range problems?” Wilfond said. “Or, do you want to have genome sequencing for all of them?”

Then there’s the results to think about.

“Just because a test tells you there’s not a problem, doesn’t mean there won’t be a problem. We just didn’t find it,” he said. And, “if we find something positive, that doesn’t mean that you will have a child with that condition.”

The research will also include an anthropologist whose job it will be to watch the doctors and the patients during this whole process to learn how the doctors’ behavior and interactions also affect patient choices and understanding.

“Not everyone wants this information, but the option can be presented in such a way that people feel like they can’t say no,” Wilfond said. “There’s uncertainty at every level.”

The reality of limited resources

Whole genome analysis is here and you can order it yourself right now, so the cat is already out of the bag …

“But it’s just a small cat or it’s just one cat,” he said. “For people who really want it, they can get the stuff, but it’s not part of routine health care.”

So, how will doctors, hospitals and insurance companies decide if this kind of testing it worth it?

“The goal of our study is to help us collectively decide if we want to put money, our money for our healthcare system, into these types of services,” he said. “Is the benefit for those who use this valuable enough that we all want to contribute to that?”

One question this study will not be big enough to answer, however, is how people will make reproductive choices based on both partners testing positive for a specific genetic problem.

The study will involve only 400 people already enrolled in Kaiser and not very many of them will test positive for a major problem and far fewer still will have a partner also test positive for the same genetic problem.

So, they won’t know if people will use the information to decide against having kids or find different partners or go to sperm/egg banks … but those studies are next.

“To me, this is an incredibly good baby step,” he said.

Would you want to know every mutation in your genome?

Yes – I want all the information I can get about my health and the potential health of my children.

No – It’s more information that I would know what to do with and I’d probably not change my behavior.